Abstract:Introduction: Venous serum and plasma are optimal specimens for serological testing but may be logistically infeasible. Dried blood spots (DBS) are a feasible alternative, provided results are adequately sensitive and specific. We aimed to assess the diagnostic accuracy of DBS to measure IgG and IgM antibodies for vaccine-preventable diseases and compare test validity of DBS with venous blood.
Areas covered:In October 2020, we searched seven databases for peer-reviewed studies assessing the diagnostic accuracy… Show more
“…DBS is not the gold standard for measurement; thus, the laboratory results might differ from the ones using whole blood samples. However, several studies have been conducted to evaluate the correlation between those results [77][78][79][80][81][82][83][84], and systematic reviews demonstrated that DBS and whole blood sampling were associated with excellent accuracy and the pooled estimates of the sensitivity and specificity for those markers were higher than 97% [85][86][87]. The laboratory results in our study are consistent with those of other studies using whole blood samples.…”
Population-based seroprevalence of chronic hepatitis B and C infections has not been examined in Lao People’s Democratic Republic (PDR). Therefore, this study aimed to estimate the seroprevalence of these infections in the general population of Lao PDR and perform subgroup analysis. A nationwide seroprevalence survey was conducted in Lao PDR in June 2019 using the multistage cluster sampling method. Dried blood spot samples were collected onto WhatmanTM 903 filter paper by finger prick. A chemiluminescent microparticle immunoassay was used to measure the levels of hepatitis B surface antigen (HBsAg) and hepatitis C antibody (HCV-Ab). Samples in which the HBsAg level was above 0.05 IU/ml and HCV-Ab was above the signal/cutoff ratio of 1.0 were considered positive based on comparisons with the relative light unit value of a calibration sample. A total of 1,927 samples (male: 47.3%, mean age: 23.0 years) were included in the analysis. The prevalence was estimated to be 4.2% (95% confidence interval [CI]: 2.7–6.3) for HBsAg and 1.6% (95% CI: 0.5–5.3) for HCV-Ab. Multivariable analysis revealed that those aged 20–24 years (adjusted odds ratio (AOR): 2.3, 95% CI: 1.1–4.6), those aged 25–29 years (AOR: 2.7, 95% CI: 1.3–5.6), those from the Northern region (AOR: 2.8, 95% CI: 1.2–6.6), and those who were Khmu (AOR: 3.6, 95% CI: 2.0–6.8) or Hmong (AOR: 5.0, 95% CI: 3.3–7.5) were significantly more likely to be positive for HBsAg. Although there were no statistically significant differences in the HCV-Ab prevalence according to each variable, males (2.9%, 95% CI: 0.7–10.7), those aged ≥40 years (6.1%, 95% CI: 2.1–16.8), and those from the Southern region (3.3%, 95% CI: 0.6–15.3) tended to have a higher prevalence. This novel population-based survey found differences in the prevalence of chronic hepatitis B and hepatitis C virus infections in Lao PDR according to sex, age group, region, and ethnicity; however, the results of this study should be confirmed in future studies, and relevant responses tailored for each target also need to be determined to control the transmission of hepatitis B and C infections.
“…DBS is not the gold standard for measurement; thus, the laboratory results might differ from the ones using whole blood samples. However, several studies have been conducted to evaluate the correlation between those results [77][78][79][80][81][82][83][84], and systematic reviews demonstrated that DBS and whole blood sampling were associated with excellent accuracy and the pooled estimates of the sensitivity and specificity for those markers were higher than 97% [85][86][87]. The laboratory results in our study are consistent with those of other studies using whole blood samples.…”
Population-based seroprevalence of chronic hepatitis B and C infections has not been examined in Lao People’s Democratic Republic (PDR). Therefore, this study aimed to estimate the seroprevalence of these infections in the general population of Lao PDR and perform subgroup analysis. A nationwide seroprevalence survey was conducted in Lao PDR in June 2019 using the multistage cluster sampling method. Dried blood spot samples were collected onto WhatmanTM 903 filter paper by finger prick. A chemiluminescent microparticle immunoassay was used to measure the levels of hepatitis B surface antigen (HBsAg) and hepatitis C antibody (HCV-Ab). Samples in which the HBsAg level was above 0.05 IU/ml and HCV-Ab was above the signal/cutoff ratio of 1.0 were considered positive based on comparisons with the relative light unit value of a calibration sample. A total of 1,927 samples (male: 47.3%, mean age: 23.0 years) were included in the analysis. The prevalence was estimated to be 4.2% (95% confidence interval [CI]: 2.7–6.3) for HBsAg and 1.6% (95% CI: 0.5–5.3) for HCV-Ab. Multivariable analysis revealed that those aged 20–24 years (adjusted odds ratio (AOR): 2.3, 95% CI: 1.1–4.6), those aged 25–29 years (AOR: 2.7, 95% CI: 1.3–5.6), those from the Northern region (AOR: 2.8, 95% CI: 1.2–6.6), and those who were Khmu (AOR: 3.6, 95% CI: 2.0–6.8) or Hmong (AOR: 5.0, 95% CI: 3.3–7.5) were significantly more likely to be positive for HBsAg. Although there were no statistically significant differences in the HCV-Ab prevalence according to each variable, males (2.9%, 95% CI: 0.7–10.7), those aged ≥40 years (6.1%, 95% CI: 2.1–16.8), and those from the Southern region (3.3%, 95% CI: 0.6–15.3) tended to have a higher prevalence. This novel population-based survey found differences in the prevalence of chronic hepatitis B and hepatitis C virus infections in Lao PDR according to sex, age group, region, and ethnicity; however, the results of this study should be confirmed in future studies, and relevant responses tailored for each target also need to be determined to control the transmission of hepatitis B and C infections.
“…This performance appears to be independent of the subsequent assays used to measure antibody levels. Excellent correlation was observed between serum and DBS for measurement of anti- Shigella antibodies by ELISA, and DBS showed excellent precision and reproducibility using multiplex bead assays [ 18 ], but there is a need for additional validation studies [ 20 ].…”
Section: Serological Testing Using Dried Blood Spotsmentioning
Background
Molecular diagnostics on human fecal samples have identified a larger burden of shigellosis than previously appreciated by culture. Evidence of fold changes in immunoglobulin G (IgG) to conserved and type-specific Shigella antigens could be used to validate the molecular assignment of type-specific Shigella as the etiology of acute diarrhea and support polymerase chain reaction (PCR)–based microbiologic end points for vaccine trials.
Methods
We will test dried blood spots collected at enrollment and 4 weeks later using bead-based immunoassays for IgG to invasion plasmid antigen B and type-specific lipopolysaccharide O-antigen for Shigella flexneri 1b, 2a, 3a, and 6 and Shigella sonnei in Shigella-positive cases and age-, site-, and season-matched test-negative controls from all sites in the Enterics for Global Health (EFGH) Shigella surveillance study. Fold antibody responses will be compared between culture-positive, culture-negative but PCR-attributable, and PCR-positive but not attributable cases and test-negative controls. Age- and site-specific seroprevalence distributions will be identified, and the association between baseline antibodies and Shigella attribution will be estimated.
Conclusions
The integration of these assays into the EFGH study will help support PCR-based attribution of acute diarrhea to type-specific Shigella, describe the baseline seroprevalence of conserved and type-specific Shigella antibodies, and support correlates of protection for immunity to Shigella diarrhea. These insights can help support the development and evaluation of Shigella vaccine candidates.
“…A variety of samples can be used for antibody detection [ 24 ]. Serological antibody detection is primarily performed on serum, but antibodies can also be measured in eluted dried-blood spots (DBS) [ 28 ], in saliva or nasal swabs for mucosal or respiratory pathogens [ 29 , 30 ] and in cerebrospinal (CSF) fluid for neurotropic pathogens [ 31 ]. Saliva sampling is increasingly seen as an attractive option since it is easy and non-invasive [ 32 , 33 , 34 , 35 ], but quantifying antibody is complicated by the absence of standardized sampling methods [ 36 ] and inherent heterogeneity of saliva protein content across individuals [ 33 ].…”
Section: Serology To Assess Disease Burdenmentioning
Understanding the local burden and epidemiology of infectious diseases is crucial to guide public health policy and prioritize interventions. Typically, infectious disease surveillance relies on capturing clinical cases within a healthcare system, classifying cases by etiology and enumerating cases over a period of time. Disease burden is often then extrapolated to the general population. Serology (i.e., examining serum for the presence of pathogen-specific antibodies) has long been used to inform about individuals past exposure and immunity to specific pathogens. However, it has been underutilized as a tool to evaluate the infectious disease burden landscape at the population level and guide public health decisions. In this review, we outline how serology provides a powerful tool to complement case-based surveillance for determining disease burden and epidemiology of infectious diseases, highlighting its benefits and limitations. We describe the current serology-based technologies and illustrate their use with examples from both the pre- and post- COVID-19-pandemic context. In particular, we review the challenges to and opportunities in implementing serological surveillance in low- and middle-income countries (LMICs), which bear the brunt of the global infectious disease burden. Finally, we discuss the relevance of serology data for public health decision-making and describe scenarios in which this data could be used, either independently or in conjunction with case-based surveillance. We conclude that public health systems would greatly benefit from the inclusion of serology to supplement and strengthen existing case-based infectious disease surveillance strategies.
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